Narrowing of cerebral blood vessels (NCBV) or cerebral vasospasm is a pathological condition that frequently develops after subarachnoid hemorrhage and leads to impairment of cerebral blood flow, cerebral oxygen delivery and subsequent cerebral ischemia and stoke. It affects up to 60% of patients with hemorrhage after rupture of intracranial aneurysms.
Cerebral vasospasm has a number of symptoms that develop gradually, including depressed level of consciousness, numbness, weakness, visual loss and increased intracranial pressure; it is usually detected by means of transcranial Doppler ultrasound and cerebral angiography. Current methods of treating cerebral vasospasm or its symptoms have been only partially successful and the approaches to prevent cerebral vasospasm so far have not been effective. Common treatments include so-called “triple H” therapy (hypertension, hypervolemia and hemodilution), intraarterial infusion of smooth muscle relaxants (papaverine, verapamil) and endovascular balloon angioplasty; prophylactic measures include calcium channel blocker administration (nimodipine). All these measures, however, do not eliminate the risks of cerebral ischemia and only marginally improve clinical outcome.
Cerebral vasospasm is a decrease in diameter of arterial vessels that supply the brain. Its frequency and to some extent severity appear to be directly related to the amount of blood in the subarachnoid space. It appears that such narrowing may, at least in the beginning, be sympathetically mediated and therefore, sympathetic blockade may theoretically prevent cerebral vasospasm development. Such blockade on systemic level, however, would be worsening the brain perfusion as it would result in lowering the patient's blood pressure.
Cerebral vasospasm typically develops between 1 and 21 days after subarachnoid hemorrhage. Therefore, all interventions to prevent and treat cerebral vasospasm preferably should be done within this timeframe.
Spinal cord stimulation (SCS) is an established modality that is widely used to treat all kinds of chronic pain, primarily neuropathic in origin. It has also been successfully used to treat most severe cases of peripheral vascular disease and intractable angina. In the latter two applications, SCS effect is not limited to pain relief but also results in vasodilatation, similar to previous experience with surgical sympathectomy.
Multiple animal experiments [7-14] have shown augmentation of cerebral blood flow (CBF) with cervical SCS. Level of stimulation seemed to have direct effect on the blood flow, with stimulation of upper levels (C1-3) generating higher flow values.
Isono et al. [9] postulated that CBF is increased from cervical SCS mainly through a central pathway. Using a cat model, they showed that CBF augmentation with cervical SCS is no longer observed after sectioning of the dorsal columns at the cervicomedullary junction. Later, Patel et al. [12] obtained the same results using rat model. The Patel group also showed lack of changes in CBF after resection of superior cervical ganglion while using SCS.
Visocchi [27] has demonstrated that SCS can either increase, decrease or has no effect in CBF. The difference correlated mainly with the stimulated level of the spinal cord. Thoracic stimulation had low effect and sometimes even decreased CBF. Cervical stimulation more frequently produced CBF augmentation (61%). In another article [28], Visocchi et al. found that vasoconstriction of carotid arteries with sympathetic trunk stimulation were attenuated by cervical SCS. In this experiment they used rabbit model to observe CBF changes with SCS alone, sympathetic trunk stimulation alone and simultaneous spinal cord and sympathetic trunk stimulation.
Patel et al. observed that increase in CBF with SCS is in direct relation with specific sympathetic receptors [11]. Their experiments demonstrated that either sympathetic ganglion blocker or al-adrenergic receptor blocker can abolish the response to SCS, but the same result does not happen with α or β-adrenergic receptor blockers.
The use of spinal cord stimulation for the treatment for cerebral vasospasm after SAH with SCS has been tried in different animal models. Ebel et al. [7] found increased blood flow in rats with SAH and SCS compared to control groups. Visocchi et al. [29] described prevention of early vasospasm in rabbits treated with SCS after induced SAH.
Recently, Lee et al. [10] showed the vasodilatation effect of SCS in the basilar artery of rats 5 days after induction of SAH. Radiotracer studies, laser Doppler flowmetry and histologic photomicrographs were used to prove these changes in the delayed spasm.
The effect of SCS on CBF in humans was first described by Hosobuchi in 1985 [30]. He found that SCS at upper cervical levels can increase CBF. The same result was not found with stimulation of thoracic levels. Later, he tested cervical SCS for patients with symptomatic cerebral ischemia in three patients (one with anterior and two with posterior circulation occlusion) [17]. Although good results were obtained, further studies were needed to confirm its clinical application.
Takanashi and Shinonaga [19] published the only article found in the literature related to the use of SCS for cerebral vasospasm in humans. Ten SAH patients with secured cerebral aneurysm (Hunt Hess grade 2 to 4 and Fisher) were implanted with percutaneous epidural cervical leads (C1-2). The stimulation was continuous and started on day 5 (±1) post bleeding for 10 to 15 days. The results were analyzed by the amount of increment in CBF with Xenon computed tomography and cerebral angiography before and after stimulation. CBF was significantly increased in the distribution of the middle cerebral artery. Four patients presented with angiographic vasospasm and 3 were reported with clinical vasospasm. One patient died and the overall outcome was good or excellent in 7. No major adverse effect was attributed to the use of SCS. The data analysis correlated increase in CBF with SCS. The electrodes were positioned all the way up to C1-2, with the intention of reaching the highest degrees of CBF augmentation.